Folate metabolism in human malaria parasites--75 years on

Area of Science:

• Tropical medicine
• Parasitology
• Drug discovery

Background:

• Malaria remains a major global health threat, with limited vaccine options necessitating reliance on antimalarial drugs.
• Existing antimalarials, including antifolates, face increasing resistance from parasite populations.
• Antifolates targeting folate metabolism are among the oldest synthetic antimalarial compounds.

Purpose of the Study:

• To review the current use of antifolates in malaria treatment.
• To discuss the mechanisms of resistance to antifolate drugs.
• To explore new insights into parasite folate metabolism for novel drug targets.

Main Methods:

• Literature review of antifolate antimalarials and malaria parasite folate metabolism.
• Analysis of current applications and resistance patterns of antifolates.
• Examination of recent advances in understanding folate pathways in the malaria parasite.

Main Results:

• Antifolates continue to be important in malaria control despite widespread resistance.
• Significant progress has been made in understanding folate metabolism and drug resistance mechanisms.
• Only two enzymes in folate metabolism have been targeted by clinical antimalarial inhibitors to date.

Conclusions:

• Understanding parasite folate metabolism offers potential for developing new antimalarial drugs.
• Further research is needed to identify and validate novel targets for antifolate-based therapies.
• Addressing drug resistance is critical for sustained malaria control efforts.